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1.
Sci Rep ; 9(1): 15839, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676878

RESUMO

Crop production, including mushroom farming, may cause significant changes to the underlying substrates which in turn, can influence crop quality and quantity during subsequent years. Here in this study, we analyzed the production of the medicinal mushroom Ganoderma lingzhi and the associated soil microbial communities and soil chemical features over 24 months from April 2015 to April 2017. This Basidiomycete mushroom, known as Lingzhi in China, is commonly found on dead trees and wood logs in temperate and subtropical forests. Its economic and medicinal importance have propelled the development of a diversity of cultivation methods. The dominant method uses wood logs as the main substrate, which after colonization by Lingzhi mycelia, are buried in the soil to induce fruiting. The soil microbial communities over the 24 months were analyzed using the Illumina HiSeq platform targeting a portion of the bacterial 16S rRNA gene and the fungal internal transcribed spacer 1 (ITS1). Overall, a significant reduction of Lingzhi yield was observed over our experimentation period. Interestingly, temporal changes in soil microbial compositions were detected during the 24 months, with the fungal community showing more changes than that of bacteria in terms of both species richness and the relative abundance of several dominant species after each fruiting. The soil chemical features also showed significant changes, with decreasing soil nitrogen and phosphorus concentrations and increasing soil pH and iron content after each fruiting. We discuss the implications of our results in sustainable Lingzhi production in soil.

2.
Mycoses ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774582

RESUMO

BACKGROUND: The sister yeast species Cryptococcus neoformans (serotype A) and Cryptococcus deneoformans (serotype D) are causative agents of deadly cryptococcosis and fungal meningoencephalitis. These haploid yeasts can hybridize in nature, giving rise to AD hybrids that are predominantly diploid or aneuploid. Despite their increasing prevalence in clinical settings, much remains unknown about the allelic distribution patterns in AD hybrid strains. OBJECTIVES: This study aims to characterize allele distributions in AD hybrids derived from the same basidium as well as from multiple basidia in a laboratory C. neoformans x C. deneoformans hybrid cross. METHODS: We dissected a total of 1625 basidiospores from 31 basidia. The 297 basidiospores that successfully germinated were genotyped by molecular characterization of 33 markers using PCR-RFLP, with at least two markers on each of the 14 chromosomes in the genome. RESULTS: 294 of the 297 strains contained at least one heterozygous locus, with a mean heterozygosity of ~30% per strain. Most hybrid genomes and chromosomes displayed significantly distorted allele distributions, with offspring originating from the same basidium tended to have alleles at different loci from the same parent. More basidia were skewed in favor of C. deneoformans alleles, the mitochondria-donor parent, than the C. neoformans alleles. CONCLUSIONS: The divergence between C. neoformans and C. deneoformans genomes has likely created co-adapted allelic combinations, with their co-segregation in hybrid offspring imparting a significant fitness benefit. However, the diversity of genotypes recovered here in a single hybridization event indicates the enormous capacity of AD hybrids for adaptation and diversification.

3.
Oncol Res ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610827

RESUMO

Apatinib, an oral small molecular receptor tyrosine kinase inhibitor (TKI) developed first in China, exerts antiangiogenic and antineoplastic function through selectively binding and inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we aimed to explore the efficacy and safety profile of apatinib monotherapy, or combined with chemotherapy or endothelial growth factor receptor (EGFR)-TKI in heavily pretreated non-small cell lung cancer (NSCLC) patients with brain metastases. We performed a retrospective analysis for relapsed NSCLC patients with brain metastases from our institute, whom received apatinib (250mg or 500mg p.o. qd) monotherapy, or combination with EGFR-TKI or chemotherapy as second- or more line systemic therapy until disease progression or unacceptable toxicity occurred. The objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS) and safety were analyzed. A total of 26 eligible patients were included: 24 patients diagnosed with adenocarcinoma, 2 with squamous carcinoma, and 14 patients harboring EGFR sensitizing mutations. The mPFS and mOS were 4.93 (range, 0.27-32.91; 95%CI 3.64-6.22) and 14.70 (range, 0.27-32.91; 95%CI 0.27-43.60) months for the whole group. The ORR and DCR were 7.7% (2/26) and 69.2% (18/26) for the entire lesions, and 7.7% (2/26) and 79.6% (20/26) for brain metastases, respectively. Compared with patients who received apatinib monotherapy, patients who received apatinib combination treatment had more favorable mPFS (11.77 vs. 2.27 months, P < 0.05) and mOS (24.03 vs. 6.07 months, P < 0.05). Treatment-related toxicities were tolerable including grade 1/2 hypertension, hand and foot syndrome, fatigue, nausea, liver dysfunction, myelosuppression, skin rash and palpitation. In conclusion, apatinib exhibited highly activity and good tolerance for NSCLC patients with brain metastasis and it might become a potential choice for metastatic brain tumors in NSCLC patients.

4.
ACS Appl Mater Interfaces ; 11(43): 40923-40931, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31588719

RESUMO

Perovskite quantum dots (PQDs) are among the most important luminescent semiconducting materials; however, they are unstable. Exposure to light, heat, and air can lead to irreversible degradation, which results in fluorescence quenching. Therefore, defects in PQDs significantly limit their practical application. Herein, we describe a simple method to enhance the photostability of CsPbBr3/nCdS QDs, which involves doping their shells with aluminum. The temperature-dependent photoluminescence (PL) of colloidal CsPbBr3/nCdS/Al2O3 QDs is investigated, and the thermal quenching of PL, blue shift of the optical band gap, and PL line width broadening are observed in each QD sample. Al2O3 layers on the CsPbBr3/nCdS QDs can effectively prevent photodegradation. Nonlinear, temperature-dependent exciton-phonon coupling and lattice dilation leads to radiative and nonradiative relaxation processes at temperatures ranging from 10 to 300 K; moreover, changes in the band gap and PL spectral line broadening are observed.

5.
Aging (Albany NY) ; 11(18): 7817-7829, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31546234

RESUMO

PRL-3, an oncogenic dual-specificity phosphatase, is overexpressed in 50% of acute myeloid leukemia patients. Stathmin has been identified as a downstream target of PRL-3 in colorectal cancer. However, the correlation between PRL-3 and stathmin in myeloid leukemia is unclear. In this study, we revealed the positive correlation between PRL-3 and stathmin in myeloid leukemia. Knockdown of the PRL-3 gene by shRNA reduced the expression of downstream stathmin, suppressed cell proliferation, induced G2/M arrest and cell apoptosis, and inhibited migration and invasion in myeloid leukemia cells. Moreover, our study was the first to provide evidence that silencing PRL-3 increased the phosphorylation level in Ser16, Ser25, Ser38, and Ser63 of stathmin, and in turn inhibited the STAT3 and STAT5 signaling in myeloid leukemia cells. This evidence points to a promoted role for PRL-3 in the progression of myeloid leukemia, and PRL-3 could be a possible new treatment target.

6.
Chin J Integr Med ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502185

RESUMO

Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flflavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1020-1025, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418351

RESUMO

OBJECTIVE: To investigate the effect of SARI overexpression on the proliferation and apoptosis of core binding factor leukemia (CBFL) cells and explore the potential molecular mechanisms. METHODS: C-KIT N822K mutation status in Kasumi-1 cell line was detected by exon 17 sequencing. Then the SARI lentiviral vector (pGC-FU-SARI) was constructed, meanwhile Kasumi-1 cells were transfected with the SARI lentiviral vector. Quantitative PCR and Western blot were employed to identify efficacy of SARI overexpression after the transfection of cells. Cells were divided into three groups, including the cells infected with pGC-FU-SARI (OE group), the cells infected with pGC-FU-GFP (NC group) and the untreated cells (blank control group). Cell proliferative activity was tested by MTT assay, cell apoptosis was measured by flow cytometry (FCM) and the expression of apoptosis-related proteins: BCL-2,BAX,Cyto C,Caspase 9,Caspase 3,cleaved-Caspase 3,PARP and cleaved-PARP as well as PI3K/Akt pathway proteins: PI3K(p85),p-PI3K(p85),Akt and p-Akt were detected by Western blot. RESULTS: The Kasumi-1 cells were detected to bear c-KIT N822K (T>A) mutation. The Kasumi-1 cells with SARI was overexpression were construeted successfully. Compared with NC group, the cell proliferation was decreased and cell apoptosis was increased; BCL-2 expression was reduced, BAX expression was enharued; cyto C expression appeared; the expression of Caspase 9 and Caspase 3 was down-regulated, the expression of cleaved Caspase 3 was up-regulated; the PARP expression was decreased, cleaved PARP expression was increased; the phosphorylation level of PI3K/Akt pathway proteins: p-PI3K/PI3K, p-Akt/Akt was down-regulated in OE group (P<0.05). CONCLUSION: SARI gene may suppress the proliferation of CBFL cells, and induce their apoptosis through the mitochondrial pathway, which may be related with the inhibition of PI3K/Akt pathway.


Assuntos
Leucemia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Ligação ao Core , Humanos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
8.
Crit Rev Food Sci Nutr ; : 1-24, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31309854

RESUMO

Diabetes mellitus (DM) is a chronic progressive systemic disease caused by a metabolic disorder. In recent years, a large number of studies have shown that certain traditional Chinese medicines and their bioactive ingredients have obvious hypoglycemic effects. This literature review focuses on medicine food homology (MFH) and medicinal health food (MHF) species used in China with a hypoglycemic function and emphasizes the bioactive ingredients and their pharmacological effects. The bioactive ingredients of MFH and MHF have been divided into six categories: saponins, flavonoids, terpenoids, alkaloids, polysaccharides, and others; and their sources, models, efficacy, and mechanisms of action have been described. It is noteworthy that the mechanisms of the bioactive ingredients of MFH and MHF with hypoglycemic effects have been summarized as follows: a) insulin-mimetic effects and restoration of the damaged pancreas; b) effect on glucose metabolism; c) increased insulin sensitivity and improved insulin resistance; and d) regulation of intestinal flora. We conclude that this review provides useful data and information to support the further investigation and application of MFH and MHF to treat DM.

9.
FEMS Microbiol Ecol ; 95(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31344232

RESUMO

Cryptococcus deneoformans is an opportunist yeast pathogen and causative agent of meningoencephalitis in humans. It is known to be mainly distributed in temperate climates. Most of our current understanding of this species has come from clinical isolates, leaving environmental populations largely unexplored. The Middle East remains one such underexplored area with no published study to date investigating cryptococcal diversity in soil. In this study, we identified 76 C. deneoformans isolates from a survey of 562 soil samples collected from six cities in Saudi Arabia. Multilocus sequence typing revealed the presence of two major sequence types (STs), ST160 (n = 63) and ST294 (n = 9), along with four singleton STs, three of which were novel. One novel ST, ST613, was likely a recombinant product between ST160 and ST294. Among the 76 isolates, 75 belonged to mating type (MAT)α while one isolate was MATa. Our analyses suggest that the Saudi Arabian C. deneoformans population likely reproduces both asexually and sexually in nature. Our study is the first to report the occurrence of C. deneoformans in a desert climate, representing a novel expansion to this species' currently known ecological niche.

10.
Mycopathologia ; 184(4): 479-492, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31309402

RESUMO

Aspergillus fumigatus is a globally distributed opportunistic fungal pathogen capable of causing highly lethal invasive aspergillosis in immunocompromised individuals. Recent studies have indicated that the global population consists of multiple, divergent genetic clusters that are geographically broadly distributed. However, most of the analyzed samples have come from continental Eurasia and the Americas where the effects of ancient versus recent factors are difficult to distinguish. Here, we investigated environmental A. fumigatus isolates from Auckland, New Zealand, a geographically isolated population, and compared them with those from other parts of the world to determine the relative roles of historical differentiation and recent gene flow in shaping A. fumigatus populations. Our data suggest that the Auckland A. fumigatus population contains both unique indigenous genetic elements as well as genetic elements that are similar to those from other regions such as Europe, Africa, and North America. Though the hypothesis of random recombination was rejected, we found abundant evidence for phylogenetic incompatibility and recombination within the Auckland A. fumigatus population. Additionally, susceptibility testing identified two triazole-resistant strains, one of which contained the globally distributed mutation TR34/L98H in the cyp51A gene. Our results suggest that contemporary gene flow, likely due to anthropogenic factors, is a major force shaping the New Zealand A. fumigatus population.

11.
BMJ Open ; 9(5): e028589, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31154312

RESUMO

OBJECTIVES: Patients' stress and satisfaction concerning cancer clinical trials (CCT) may affect study accrual and quality. Our study aimed to evaluate stress and satisfaction in CCT and the influencing factors. DESIGN: Cross-sectional analysis done by a questionnaire after informed consent. SETTING: Cancer Hospital, Chinese Academy of Medical Sciences. PARTICIPANTS: 199 CCT participants. Primary and secondary outcome measures self-assessed stress and satisfaction in CCT. RESULTS: Among 199 participants, 83.9% would join CCT again; 72.9% had enough time to decide on trial participation; 73.9% claimed complete awareness of CCT; 3.5% doubted CCT's significance and scientific quality; 33.2% deemed CCT time-consuming; 73.9% scored satisfaction ≥9/10; and 25.6% claimed moderate to severe stress. Positive factors for satisfaction were enough decision time (OR=0.36, p=0.0003), better impressions of doctors (OR=0.41, p=0.047) and less time-consuming trials (OR=0.43, p<0.0001). Individuals with more prior uninsured medical expenses (OR=1.23, p=0.026), less time consumption (OR=2.35, p<0.0001) and more tests in CCT (OR=0.64, p=0.035) were less likely to experience stress. Phase III study participants bore less stress than phase II (OR=0.29, p=0.032) but more than phase I (OR=1.18, p=0.009). CONCLUSIONS: Our study addressed factors influencing CCT participants' stress and satisfaction. We suggested measures to improve patients' experiences in CCT. TRIAL REGISTRATION NUMBER: NCT03412344; Pre-results.

12.
Int J Med Sci ; 16(5): 757-765, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217744

RESUMO

Background: The D816V mutation of c-KIT can constitutively activate tyrosine kinase, thereby promote core binding factor acute myeloid leukemia (CBF-AML) cell proliferation and inhibit apoptosis. Previous studies have indicated similar proliferation and apoptosis between N822K and D816V mutations.The current study aims to determine the occurrence and potential functions of N822K mutation-induced c-KIT activation in AML cells, and explore possible mechanisms of poor prognosis of CBF-AML. Methods: c-KIT N822K mutation status in AML cells was determined by exon 17 sequencing. The level of c-KIT expression was detected by flow cytometry (FCM) and colony formation was assessed after hu-SCF stimulation. After exposure to sunitinib (a kind of tyrosine kinase inhibitor, TKI), cell proliferation inhibition was tested by MTT, cell cycle and apoptosis were measured by FCM, autophagy was assessed by fluorescence microscopy and immunoblotting. Results: Kasumi-1 cell line was detected to bear c-KIT N822K (T>A) mutation. After hu-SCF stimulation, CD117 expression was decreased and the colony formation efficiency was not altered in Kasumi-1 cells. After sunitinib inhibited the c-KIT activity, the colony formation efficiency was reduced, and the half-maximal inhibitory concentration (IC50) of sunitinib was low (0.44±0.17µM) at 48 hours. Moreover, cells were arrested in G0/G1 phase, corresponding to an increase of apoptosis ratio. Acidic vesicular organelles (AVO) were observed along with an altered expression of autophagy-related proteins in Kasumi-1 cells. Conclusions: Our data indicated that inhibition of N822K T>A mutation-induced constitutive c-KIT activation in AML cells triggered apoptotic and autophagic pathways leading to death, and c-KIT N822K mutation may have clinical application as a CBF-AML treatment target.

13.
Opt Express ; 27(12): 16550-16559, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31252879

RESUMO

Reconfigurable design is an effective way to achieve multifunctional devices for system integration. Limited by the feeding network for multi-resonators, multimode absorbers with more than four modes are rarely reported. In this paper, a frequency-reconfigurable metamaterial absorber/reflector resonating at 3.05, 4.45 and 5.54 GHz is proposed. Based on a stereoscopic feeding network and a strategic arranged structure with loaded switching diodes, the proposed structure can realize the reconfigurable eight operating modes, including triple-band (111)/dual-band (110, 101, 011)/single-band (100, 010, 001) absorption and reflection (000) without re-optimizing and re-engineering the structure. The simulated results are confirmed by measuring a fabricated prototype. Our design provides a strategy to realize multifunction devices in microwave or even higher frequencies.

14.
Nat Commun ; 10(1): 2602, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197136

RESUMO

Temperature is a key factor for determining the lifespan of both poikilotherms and homeotherms. It is believed that animals live longer at lower body temperatures. However, the precise mechanism remains largely unknown. Here, we report that autophagy serves as a boost mechanism for longevity at low temperature in the nematode Caenorhabditis elegans. The adiponectin receptor AdipoR2 homolog PAQR-2 signaling detects temperature drop and augments the biosynthesis of two ω-6 polyunsaturated fatty acids, γ-linolenic acid and arachidonic acid. These two polyunsaturated fatty acids in turn initiate autophagy in the epidermis, delaying an age-dependent decline in collagen contents, and extending the lifespan. Our findings reveal that the adiponectin receptor PAQR-2 signaling acts as a regulator linking low temperature with autophagy to extend lifespan, and suggest that such a mechanism may be evolutionally conserved among diverse organisms.


Assuntos
Autofagia/fisiologia , Proteínas de Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/fisiologia , Longevidade/fisiologia , Proteínas de Membrana/fisiologia , Animais , Animais Geneticamente Modificados , Ácido Araquidônico/biossíntese , Temperatura Baixa , Colágeno/metabolismo , Epiderme/metabolismo , Ácidos Graxos Ômega-6/biossíntese , Interferência de RNA , Transdução de Sinais/fisiologia
15.
Ann Thorac Surg ; 108(4): 1127-1132, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31075249

RESUMO

BACKGROUND: The outcomes of surgical treatment of ventricular septal rupture (VSR) complicating acute myocardial infarction are worse in patients with cardiogenic shock. This study aimed to identify clinical characteristics and outcomes in patients with VSR presenting with cardiogenic shock. METHODS: A retrospective analysis was performed in 105 consecutive VSR patients, 71 with cardiogenic shock (67.6%) and 34 without cardiogenic shock (32.4%), who underwent surgical treatment in the Department of Adult Cardiac Surgery of Fuwai Hospital between January 2002 and December 2017. Baseline characteristics and outcomes in patients with VSR with and without cardiogenic shock were assessed. RESULTS: There were no differences in hypertension, diabetes, history of myocardial infarction, body mass index, or location of VSR between patients with and without cardiogenic shock. The size of VSR was larger in patients with cardiogenic shock than in those without (18.2 ± 8.1 mm vs 14.0 ± 7.8 mm; P = .013). Intraaortic balloon pump was required more in patients with cardiogenic shock before operation (39 [68.4%] vs 1 [5.0%]; P < .001]. More emergency surgeries were performed in the cardiogenic shock group (21 [29.6%] vs 3 [8.8%]; P = .018). There were 3 in-hospital deaths among patients with VSR with cardiogenic shock. After 76.56 ± 47.78 months of follow-up, only 2 noncardiac deaths were documented. CONCLUSIONS: The larger the ventricular septal rupture is, the more prone patients are to develop cardiogenic shock. Surgical treatment outcomes for VSR with cardiogenic shock are satisfactory.

17.
Fungal Biol ; 123(4): 274-282, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30928036

RESUMO

The fungus Purpureocillium lavendulum (formally Paecilomyces lilacinus) is a natural enemy of insects and plant-parasitic nematodes, and has been used as an important bio-control agent against agricultural pests all over the world. In order to understand the genetic mechanisms governing its biocontrol efficiency and other biological processes, an effective gene disruption system is needed. Here we report the development of an efficient system which integrates selective markers that differ from Purpureocillium lilacinum, a one-step construction method for gene knockout plasmids, and a ku80 knockout strain for efficient homologous recombination. With this system, we effectively disrupted the transcription factors in the central regulation pathway of sporulation and a serine protease which were contributed to nematode infection, demonstrating this system as an efficient gene disrupting system for further characterization of genes involved in the development and pathogenesis of this fungus.


Assuntos
Técnicas de Inativação de Genes/métodos , Genética Microbiana/métodos , Hypocreales/genética , Biologia Molecular/métodos , Vetores Genéticos , Recombinação Homóloga , Plasmídeos , Seleção Genética
18.
Philos Trans R Soc Lond B Biol Sci ; 374(1767): 20180317, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30967028

RESUMO

Plant-parasitic nematodes (PPNs) cause severe damage to agricultural crops worldwide. As most chemical nematicides have negative environmental side effects, there is a pressing need for developing efficient biocontrol methods. Nematophagous microbes, the natural enemies of nematodes, are potential biocontrol agents against PPNs. These natural enemies include both bacteria and fungi and they use diverse methods to infect and kill nematodes. For instance, nematode-trapping fungi can sense host signals and produce special trapping devices to capture nematodes, whereas endo-parasitic fungi can kill nematodes by spore adhesion and invasive growth to break the nematode cuticle. By contrast, nematophagous bacteria can secrete virulence factors to kill nematodes. In addition, some bacteria can mobilize nematode-trapping fungi to kill nematodes. In response, nematodes can also sense and defend against the microbial pathogens using strategies such as producing anti-microbial peptides regulated by the innate immunity system. Recent progresses in our understanding of the signal pathways involved in microbe-nematode interactions are providing new insights in developing efficient biological control strategies against PPNs. This article is part of the theme issue 'Biotic signalling sheds light on smart pest management'.

19.
Respir Physiol Neurobiol ; 266: 9-17, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31022471

RESUMO

Cigarette smoke (CS) is a risk factor for pulmonary fibrosis and lipopolysaccharides (LPS) are associated with human occupational lung diseases; however, their combined role in pulmonary fibrosis remains unknown. Therefore, we investigated whether CS combined with LPS induces pulmonary fibrosis in mice. C57BL/6 mice were exposed to CS or normal air for 21 or 35 days, followed by LPS or saline instillation on day 14, 21, and 28. Lung function was tested, and lung tissues were harvested for histological and molecular analyses. Compared to the control, CS and LPS groups, the CS + LPS group showed reduced body weight and survival rate, increased respiratory resistance, decreased lung compliance, marked alveolar structure destruction, and fibrotic lesion formation. Lung tissues showed a considerable increase in IL-6, TNF-α, IL-1ß, α-SMA, and TGF-ß levels and collagen content. Our results indicate that cigarette smoke exposure followed by LPS in mice induces pulmonary fibrosis with pathophysiology consistent with that of human pulmonary fibrosis.

20.
Mycopathologia ; 184(2): 195-212, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30891668

RESUMO

The Cryptococcus neoformans species complex is a model organism for fungal studies. Many studies have used two strains, JEC20 and JEC21, and their derivatives. These two strains were obtained through 10 rounds of backcrosses and have been assumed near identical except at the mating-type locus. Here we obtained and compared the JEC20 genome sequence with the published "JEC21" genome. Our comparison revealed 5322 single nucleotide polymorphisms (SNPs) with the majority (N = 3816, 71.7%) located in three genomic regions, including the previously noted mating-type region. The remaining 1506 SNPs (28.3%) were distributed throughout all 14 chromosomes, predominantly at chromosomal ends. To study the potential effects of these three SNP-rich regions on phenotypes, 24 progenies from the JEC20 × JEC21 cross representing eight recombinant genotypes were analyzed for their mating ability, melanin production, capsule formation, and growths at 30 °C and 40 °C. Significant phenotypic variations were found among the progeny. However, the observed phenotypic variations could not be explained by the three SNP-rich regions. Further genome sequencing of our JEC21 and the 24 progenies revealed only six segregating SNPs outside of the three SNP-rich regions between JEC20 and JEC21, a result indicating that the 1500 SNPs identified in the published "JEC21" genome might be caused by sequencing errors and/or strain mixing. However, the six SNPs and the three SNP-rich regions could not explain the observed phenotypic variations. Our analyses suggest that spontaneous mutations accumulated under laboratory conditions could have significant effects on phenotypes and on our interpretations of experimental results.


Assuntos
Cryptococcus neoformans/crescimento & desenvolvimento , Cryptococcus neoformans/genética , Genômica , Mutação , Polimorfismo de Nucleotídeo Único , Biologia Computacional , Cruzamentos Genéticos , Cryptococcus neoformans/metabolismo , Genótipo , Melaninas/metabolismo , Polissacarídeos/metabolismo , Recombinação Genética , Análise de Sequência de DNA , Temperatura Ambiente , Sequenciamento Completo do Genoma
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